Abstract

Background. Lapatinib is an oral small molecule dual tyrosine kinase inhibitor that binds intracellularly to the ATP binding site of the EGFR and HER2 receptors. In a randomized controlled trial (RCT) of women with HER2+ metastatic breast cancer (MBC) previously treated with trastuzumab, an anthracycline, and taxanes, lapatinib plus capecitabine improved time to progression versus capecitabine monotherapy. In an RCT of postmenopausal women with HR+ MBC, 1st-line therapy with lapatinib plus letrozole improved progressionfree survival vs. letrozole monotherapy in the primary analysis HER2+ population. Data on adherence and persistence with lapatinib in typical clinical practice are unavailable.

Methods. This was retrospective observational study of adherence and persistence with lapatinib in women with MBC who were previously treated with trastuzumab. Data were from the Thomson MedStat MarketScan® Commercial and Medicare health insurance claims databases spanning 1/2000-3/2010 and representing >90 million covered lives. Subjects included women with ≥1 claims with a diagnosis of breast cancer, ≥1 claims with a diagnosis of distant metastases, ≥1 trastuzumab claim after first distant metastases diagnosis, and ≥1 lapatinib claim after first trastuzumab claim (date of first lapatinib claim="index date”). Pts with <12 mos. continuous enrollment pre-index or <3 mos. continuous enrollment post-index were excluded. Measures of lapatinib adherence and persistence were calculated from days supplied information on pharmacy claims and included medication possession ratio (MPR), time to discontinuation (end of supply), time to first treatment interruption (gap during treatment of ≥30 days without supply), and duration of continuous therapy (time to gap of ≥30 days without supply or end of supply).

Results. A total of 1299 pts had ≥1 claims with a diagnosis of breast cancer, ≥1 claims with a diagnosis of distant metastases, ≥1 claims for trastuzumab, and ≥1 claims for lapatinib (1106 Commercial, 93 Medicare). Of these, 666 met all inclusion criteria (572 Commercial, 94 Medicare). Mean (SD) age was 52 (8) years in Commercial pts and 72 (6) years in Medicare pts. Among all pts, 73% had claims history of prior taxanes, 27% prior anthracylines, and 24% prior taxanes and prior anthracyclines. Mean (SD) initial lapatinib dosage was 1161 (339) mg daily; 84% initiated lapatinib on 1250 mg daily. Sixty-three percent received index lapatinib in combination with capecitabine; 6% in combination with an aromatase inhibitor. Median follow-up was 12 mos. Mean (SD) number of lapatinib claims was 7.1 (4.9). Mean (SD) MPR was 87% (19%); median MPR was 96%. Kaplan-Meier estimated median time to discontinuation of lapatinib was 7.4 months (95%CI 6.7−8.0 mos). Seventy three percent of patients had no treatment interruption during follow-up. Median duration of continuous therapy was 5.2 mos (95%CI 4.8−5.7 mos).

Conclusions. In women with MBC previously-treated with trastuzumab, adherence and persistence with lapatinib in typical clinical practice are relatively high. Further research is needed to identify predictors and consequences of non-adherence so that efforts may be targeted to enhance adherence to effective treatment.